Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma.
eQTL
glaucoma
human induced pluripotent stem cells
retinal ganglion cells
retinal organoids
single-cell RNA sequencing
transcriptomics
Journal
Cell genomics
ISSN: 2666-979X
Titre abrégé: Cell Genom
Pays: United States
ID NLM: 9918284260106676
Informations de publication
Date de publication:
08 Jun 2022
08 Jun 2022
Historique:
received:
19
09
2020
revised:
08
03
2021
accepted:
11
05
2022
entrez:
13
2
2023
pubmed:
14
2
2023
medline:
14
2
2023
Statut:
epublish
Résumé
To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared with those from healthy individuals. We performed single-cell RNA sequencing of a total of 247,520 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 4,443 significant loci across all cell types, 312 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 97 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease.
Identifiants
pubmed: 36778138
doi: 10.1016/j.xgen.2022.100142
pii: S2666-979X(22)00075-1
pmc: PMC9903700
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100142Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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